Convection-enhanced delivery of tumor necrosis factor-related apoptosis-inducing ligand with systemic administration of temozolomide prolongs survival in an intracranial glioblastoma xenograft model
Convection-enhanced delivery of tumor necrosis factor-related apoptosis-inducing ligand with systemic administration of temozolomide prolongs survival in an intracranial glioblastoma xenograft model
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DOI：
10.1158/0008-5472.can-04-1683
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发表时间：
2004-10-01
期刊：
影响因子：
11.2
通讯作者：
Bankiewicz, KS
中科院分区：
文献类型：
--
作者：
Saito, R;Bringas, JR;Bankiewicz, KS
尽管肿瘤坏死因子相关凋亡诱导配体（TRAIL）是细胞死亡的有效激活剂，优先杀死肿瘤细胞而不是正常细胞，但是由于细胞抗性以及重要的是全身给药后的不良分布，TRAIL用于治疗胶质瘤的功效可能是有限的。TRAIL和替莫唑胺（TMZ）最近被证明在体外对U87 MG胶质瘤细胞具有协同抗肿瘤作用。对流增强递送（CED）可以有效地将TRAIL蛋白分布在整个脑肿瘤块中。在这项研究中，我们评估了CED的TRAIL，单独和与全身TMZ管理，抗肿瘤疗效。TRAIL的CED在正常脑和U87MG颅内异种移植物模型中均表现出安全有效的分布。单独地，CED的TRAIL和全身TMZ给药延长了荷瘤大鼠的生存期。然而，这两种治疗的组合比单独治疗更有效。CED的TRAIL结合全身TMZ治疗是一种有前途的策略，用于治疗恶性胶质瘤。
Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent activator of cell death, preferentially killing neoplastic cells over normal cells, the efficacy of TRAIL for the treatment of glioma might be limited due to cellular resistance and, importantly, poor distribution after systemic administration. TRAIL and temozolomide (TMZ) were recently shown to have a synergistic antitumor effect against U87MG glioma cells in vitro. Convection-enhanced delivery (CED) can effectively distribute TRAIL protein throughout a brain tumor mass. In this study, we evaluated CED of TRAIL, alone and in conjunction with systemic TMZ administration, for antitumor efficacy. CED of TRAIL demonstrated safe and effective distribution in both normal brain and a U87MG intracranial xenograft model. Individually, both CED of TRAIL and systemic TMZ administration prolonged survival in tumor-bearing rats. However, the combination of these two treatments was significantly more effective than either treatment alone. CED of TRAIL in conjunction with systemic TMZ treatment is a promising strategy for the treatment of malignant gliomas.